In recent years, leukocyte-free blood transfusion in which leukocytes contained in a blood product are removed in advance is increasingly applied in the field of blood transfusion. This is due to the finding that the side effects such as headache, nausea, chills, and an anhemolytic exothermic reaction, as well as heavy side effects such as alloantigen sensitization, viral infection, and post-blood transfusion graft-versus-host disease (GVHD) are mainly induced by leukocytes contained in blood products used for transfusion.
The methods for removing leukocytes from a blood product may be roughly classified into two kinds of methods of a centrifugal method in which leukocytes are separated and removed using a centrifuge by utilizing the difference in specific gravity among blood components, and a filtering method in which leukocytes are removed using a filter material formed of a fiber assembly, such as nonwoven fabric or the like, or a porous structure having continuous pores by utilizing adhesion of the leukocytes to the filter material or a sieve effect achieved by the pores of the filter material. Of these the filtering method has been widely used due to advantages such as simple operation, low cost, and excellent leukocyte-removing capability.
Most of the leukocyte-removing filter apparatuses which are now commercially available include a plurality of types of filter materials. An aggregate-removing filter material of loose texture that removes aggregates contained in a blood product is disposed in the upstream area near the blood inlet. A leukocyte-removing filter material of fine texture that removes leukocytes is disposed in the downstream area near the blood outlet side. Aggregates are formed by aggregating erythrocytes, leukocytes, platelets, fibrin, fibrinogen, other denatured proteins, fat globules and the like. Aggregates have diversity, including relatively small aggregates referred to as “microaggregates” having a size almost equal to that of leukocytes to about several tens of micrometers, and large aggregates referred to as “macroaggregates” having a size larger than about several tens of micrometers, for example exceed 1 mm, and the aggregates have high adhesion property. The number and the size of aggregates tend to increase as longer the storage period of the blood product and/or lower the storage temperature is. Therefore, when filtering a blood product using only a leukocyte-removing filter material without using an aggregate-removing filter material, the leukocyte-removing filter material clogs by aggregates, thereby being difficult to maintain the desired flow rate.
In order to deal with the above problem, Patent Document 1 discloses a filter apparatus that includes two or more types of aggregate-removing filter materials being selected from the group consisting of a nonwoven fabric, a woven fabric and a knitted fabric, and each having differ bulk density within the range of 0.1 to 1.0 g/cm3 and the filter materials are disposed on the upstream side of a leukocyte-removing filter material so as to increase the bulk density of the aggregate-removing filter materials toward the downstream side.
Patent Document 2 discloses a filter apparatus that includes a plurality of types of fibers, wherein the product XY of the average fiber diameter X and the average fiber to fiber distance Y is specified. In Patent Document 2, a filter material with XY>50 is disposed upstream of the filter apparatus to capture relatively large aggregates, a filter material with 50≧XY>7 is disposed downstream of the filter material with XY>50 to capture relatively small aggregates, and a filter material with 7≧XY is disposed further downstream of the filter material with 50≧XY>7 to remove leukocytes.
Patent Document 3 discloses an aggregate-removing filter material that has at least two types of pore-groups including pore-group A having a pore size of 500 μm or more and an average pore diameter of 600 to 1500 μm and pore-group B having a pore size of 150 to 500 μm and an average pore diameter of 200 to 450 μm, and that the porosity of the filter material is 40% or more.
Patent Document 4 discloses a filter apparatus that includes the first to third elements, wherein the first element is a filter material that removes gel (which is synonymous word of large aggregates (macroaggregates)), the second element is a filter material that removes microaggregates, and the third element is a filter material that removes leukocytes.